Colony stimulating factor-1 (CSF-1) regulates the survival, proliferation and differentiation of mononuclear phagocytes and appears to play an important role in the formation and/or maintenance of the placenta, via its receptor, a 165 kDa tyrosine kinase which is identical to the c-fms proto-oncogene product. It is proposed to study the mechanism of CSF-1 action in vitro and in vivo. The biochemical events associated with the rapid, CSF-l induced increase in the tyrosine phosphorylation of cytoplasmic and membrane proteins in intact cells will be studied. The components involved will be identified, and if novel, their genes cloned to aid the analysis of the role of the proteins in CSF-1 signal transduction. Among other approaches, mutants of a CSF-1 responsive macrophage cell line, that are defective in their response to CSF-l, will be used to determine which of the early events are involved in particular arms of the pleiotropic response to the growth factor, particularly the mitogenic response. In addition, the distribution, function and relationship between cells synthesizing CSF-l and cells expressing the CSF-l receptor will be investigated.